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ABSTRACT: 1 H-NMR metabolomics-derived biomarkers maltose, acetate, formate, and lactate have excellent potential as predictive biomarkers for bacterial vaginosis with an area under curve of 0.97 (95% confidence interval, 0.88-1.00), sensitivity of 0.90, and specificity of 0.95.
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Vaginosis Bacteriana , Femenino , Humanos , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/microbiología , Metabolómica , Biomarcadores , AcetatosRESUMEN
Body fluids, cells, and tissues contain a wide variety of metabolites that consist of a mixture of various low-molecular-weight compounds, including amino acids, peptides, lipids, nucleic acids, and organic acids, which makes comprehensive analysis more difficult. Quantitative nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical technique for analyzing the metabolic profiles of body fluids, cells, and tissues. It enables fast and comprehensive detection, characterization, a high level of experimental reproducibility, minimal sample preparation, and quantification of various endogenous metabolites. In recent times, NMR-based metabolomics has been appreciably utilized in diverse branches of medicine, including microbiology, toxicology, pathophysiology, pharmacology, nutritional intervention, and disease diagnosis/prognosis. In this review, the utility of NMR-based metabolomics in clinical studies is discussed. The significance of in vitro NMR-based metabolomics as an effective tool for detecting metabolites and their variations in different diseases are discussed, together with the possibility of identifying specific biomarkers that can contribute to early detection and diagnosis of disease.
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Imagen por Resonancia Magnética , Metabolómica , Reproducibilidad de los Resultados , Espectroscopía de Resonancia Magnética/métodos , Metabolómica/métodos , MetabolomaRESUMEN
The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture-confirmed intra-thoracic TB (ITTB) (n = 23) and compared it with those of non-TB controls (NTCs) (n = 13) using proton NMR spectroscopy-based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N-α-acetyl-lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti-inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population.
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Current challenges of using serum prostate-specific antigen (PSA) level-based screening, such as the increased false positive rate, inability to detect clinically significant prostate cancer (PCa) with random biopsy, multifocality in PCa, and the molecular heterogeneity of PCa, can be addressed by integrating advanced multiparametric MR imaging (mpMRI) approaches into the diagnostic workup of PCa. The standard method for diagnosing PCa is a transrectal ultrasonography (TRUS)-guided systematic prostate biopsy, but it suffers from sampling errors and frequently fails to detect clinically significant PCa. mpMRI not only increases the detection of clinically significant PCa, but it also helps to reduce unnecessary biopsies because of its high negative predictive value. Furthermore, non-Cartesian image acquisition and compressed sensing have resulted in faster MR acquisition with improved signal-to-noise ratio, which can be used in quantitative MRI methods such as dynamic contrast-enhanced (DCE)-MRI. With the growing emphasis on the role of pre-biopsy mpMRI in the evaluation of PCa, there is an increased demand for innovative MRI methods that can improve PCa grading, detect clinically significant PCa, and biopsy guidance. To meet these demands, in addition to routine T1-weighted, T2-weighted, DCE-MRI, diffusion MRI, and MR spectroscopy, several new MR methods such as restriction spectrum imaging, vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) method, hybrid multi-dimensional MRI, luminal water imaging, and MR fingerprinting have been developed for a better characterization of the disease. Further, with the increasing interest in combining MR data with clinical and genomic data, there is a growing interest in utilizing radiomics and radiogenomics approaches. These big data can also be utilized in the development of computer-aided diagnostic tools, including automatic segmentation and the detection of clinically significant PCa using machine learning methods.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
Nuclear magnetic resonance (NMR) metabolomics is a powerful analytical technique and a tool which has unique characteristics and capabilities for the evaluation of a number of biochemicals/metabolites of cancer and other disease processes that are present in biofluids (urine and blood) and tissues. The potential of NMR metabolomics in prostate cancer (PCa) has been explored by researchers and its usefulness has been documented. A large number of metabolites such as citrate, choline, and sarcosine were detected by NMR metabolomics from biofluids and tissues related to PCa and their levels were compared with controls and benign prostatic hyperplasia. The changes in the levels of these metabolites aid in the diagnosis and help to understand the dysregulated metabolic pathways in PCa. We review recent studies on in vitro and ex vivo NMR spectroscopy-based PCa metabolomics and its possible role as a diagnostic tool.
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Involvement of visual cortex varies during tactile perception tasks in early blind (EB) and late blind (LB) human subjects. This study explored differences in sensory motor networks associated with tactile task in EB and LB subjects and between children and adolescents. A total of 40 EB subjects, 40 LB subjects, and 30 sighted controls were recruited in two subgroups: children (6-12 years) and adolescents (13-19 years). Data were acquired using a 3T MR scanner. Analyses of blood oxygen level dependent (BOLD), functional connectivity (FC), correlation, and post hoc test for multiple comparisons were carried out. Difference in BOLD activity was observed in EB and LB groups in visual cortex during tactile perception, with increased FC of visual with dorsal attention and sensory motor networks in EB. EB adolescents exhibited increased connectivity with default mode and salience networks when compared with LB. Functional results correlated with duration of training, suggestive of better performance in EB. Alteration in sensory and visual networks in EB and LB correlated with duration of tactile training. Age of onset of blindness has an effect in cross-modal reorganization of visual cortex in EB and multimodal in LB in children and adolescents.
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Percepción del Tacto , Corteza Visual , Adolescente , Ceguera , Corteza Cerebral , Niño , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Functional network changes associated with Braille reading are different in early blind (EB) and late blind (LB) participants. The objectives were to study the functional connectivity (of memory and language areas based on blood oxygen level-dependent [BOLD] mapping) and structural changes in EB and LB children and adolescents. A total of 110 participants (all right-handed) were recruited in two age groups of 6-12 years (children) and 13-19 years (adolescents) consisting of EB (n = 20), LB (n = 20), and sighted controls (SC, n = 15) in each group. Group differences were estimated between children and adolescent groups. Structural changes in visual cortex and medial temporal area, increased BOLD activations and altered functional connectivity in the primary visual cortex, inferior frontal gyrus, middle temporal gyrus, and hippocampus during Braille reading task were observed in adolescents as compared with children blind groups (pFDR corrected <0.05). Functional results were positively correlated with duration of Braille reading and age at onset in EB and LB groups (p ≤ 0.01). Visual, language, and learning memory networks were different in adolescents and children of both EB and LB groups, and also between EB and LB groups suggesting cross-modal plasticity. The functional and structural results revealed education dependent cross-modal plasticity in visually impaired participants. Memory and language network were affected more in the LB group than the EB group, and more in children than adolescents.
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Celiac disease (CeD) is an autoimmune enteropathy caused by gluten intake in genetically predisposed individuals. We investigated the metabolism of CeD by metabolic profiling of intestinal mucosa, blood plasma and urine using NMR spectroscopy and multivariate analysis. The metabolic profile of the small intestinal mucosa was compared between patients with CeD (n = 64) and disease controls (DCs, n = 30). The blood plasma and urinary metabolomes of CeD patients were compared with healthy controls (HCs, n = 39). Twelve metabolites (proline (Pro), arginine (Arg), glycine (Gly), histidine (His), glutamate (Glu), aspartate, tryptophan (Trp), fumarate, formate, succinate (Succ), glycerophosphocholine (GPC) and allantoin (Alln)) of intestinal mucosa differentiated CeD from controls. The metabolome of blood plasma with 18 metabolites (Pro, Arg, Gly, alanine, Glu, glutamine, glucose (Glc), lactate (Lac), acetate (Ace), acetoacetate (AcAc), ß-hydroxybutyrate (ß-OHB), pyruvate (Pyr), Succ, citrate (Cit), choline (Cho), creatine (Cr), phosphocreatine (PCr) and creatinine) and 9 metabolites of urine (Pro, Trp, ß-OHB, Pyr, Succ, N-methylnicotinamide (NMN), aminohippurate (AHA), indoxyl sulfate (IS) and Alln) distinguished CeD from HCs. Our data demonstrated changes in nine metabolic pathways. The altered metabolites were associated with increased oxidative stress (Alln), impaired healing and repair mechanisms (Pro, Arg), compromised anti-inflammatory and cytoprotective processes (Gly, His, NMN), altered energy metabolism (Glc, Lac, ß-OHB, Ace, AcAc, Pyr, Succ, Cit, Cho, Cr and PCr), impaired membrane metabolism (GPC and Cho) and intestinal dysbiosis (AHA and IS). An orthogonal partial least square discriminant analysis model provided clear differentiation between patients with CeD and controls in all three specimens. A classification model built by combining the distinguishing metabolites of blood plasma and urine samples gave an AUC of 0.99 with 97.7% sensitivity, 93.3% specificity and a predictive accuracy of 95.1%, which was higher than for the models built separately using small intestinal mucosa, blood plasma and urine. In conclusion, a panel of metabolic biomarkers in intestinal biopsies, plasma and urine samples has potential to differentiate CeD from controls and may complement traditional tests to improve the diagnosis of CeD.
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Enfermedad Celíaca/metabolismo , Mucosa Intestinal/metabolismo , Espectroscopía de Resonancia Magnética , Metaboloma , Adolescente , Adulto , Aminoácidos/análisis , Aminoácidos/sangre , Aminoácidos/orina , Biopsia , Enfermedad Celíaca/sangre , Enfermedad Celíaca/orina , Dispepsia/metabolismo , Femenino , Reflujo Gastroesofágico/metabolismo , Humanos , Mucosa Intestinal/química , Intestino Delgado/química , Intestino Delgado/metabolismo , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
In the last two decades, various in vivo MR methodologies have been evaluated for their potential in the study of cancer metabolism. During malignant transformation, metabolic alterations occur, leading to morphological and functional changes. Among various MR methods, in vivo MRS has been extensively used in breast cancer to study the metabolism of cells, tissues or whole organs. It provides biochemical information at the metabolite level. Altered choline, phospholipid and energy metabolism has been documented using proton (1 H), phosphorus (31 P) and carbon (13 C) isotopes. Increased levels of choline-containing compounds, phosphomonoesters and phosphodiesters in breast cancer, which are indicative of altered choline and phospholipid metabolism, have been reported using in vivo, in vitro and ex vivo NMR studies. These changes are reversed on successful therapy, which depends on the treatment regimen given. Monitoring the various tumor intermediary metabolic pathways using nuclear spin hyperpolarization of 13 C-labeled substrates by dynamic nuclear polarization has also been recently reported. Furthermore, the utility of various methods such as diffusion, dynamic contrast and perfusion MRI have also been evaluated to study breast tumor metabolism. Parameters such as tumor volume, apparent diffusion coefficient, volume transfer coefficient and extracellular volume ratio are estimated. These parameters provide information on the changes in tumor microstructure, microenvironment, abnormal vasculature, permeability and grade of the tumor. Such changes seen during cancer progression are due to alterations in the tumor metabolism, leading to changes in cell architecture. Due to architectural changes, the tissue mechanical properties are altered; this can be studied using magnetic resonance elastography, which measures the elastic properties of tissues. Moreover, these structural MRI methods can be used to investigate the effect of therapy-induced changes in tumor characteristics. This review discusses the potential of various in vivo MR methodologies in the study of breast cancer metabolism.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Imagen por Resonancia Magnética , Colina/metabolismo , Medios de Contraste/química , Femenino , Humanos , Modelos Biológicos , Vía de Señalización WntRESUMEN
Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post-MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.
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Isquemia Encefálica/tratamiento farmacológico , Citalopram/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Prueba de Desempeño de Rotación con Aceleración Constante , Accidente Cerebrovascular/metabolismoRESUMEN
BACKGROUND: Risk calculators have traditionally utilized serum prostate-specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa). PURPOSE: To develop a prebiopsy multiparametric MRI (mpMRI)-based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy-naive men with serum PSA between 4-10 ng/mL that may help reduce unnecessary biopsies. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: In all, 137 consecutive men with PSA between 4-10 ng/mL underwent prebiopsy mpMRI (diffusion-weighted [DW]-MRI and MR spectroscopic imaging [MRSI]) during 2009-2015 were recruited for this study. FIELD STRENGTH/SEQUENCE: 1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1 -weighted, T2 -weighted, DW-MRI, and MRSI sequences were used. ASSESSMENT: All eligible patients underwent mpMRI-directed, cognitive-fusion transrectal ultrasound (TRUS)-guided biopsies. STATISTICAL TESTS: An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10-fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters. RESULTS: Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6-point mpMRI-based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24-6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis. DATA CONCLUSION: A statistical equation and a simple 6-point mpMRI-based RS can be used as a point-of-care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1227-1236.
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Imagen de Difusión por Resonancia Magnética , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Área Bajo la Curva , Artefactos , Estudios Transversales , Humanos , Biopsia Guiada por Imagen/métodos , Masculino , Persona de Mediana Edad , Movimiento (Física) , Análisis Multivariante , Estudios Prospectivos , Próstata/patología , Curva ROC , Medición de Riesgo , EspectrofotometríaRESUMEN
BACKGROUND & AIMS: Data on minimal hepatic encephalopathy (MHE) in children is scarce. We aimed to study MHE in children with chronic liver disease (CLD) and to validate non-invasive objective tests which can assist in its diagnosis. METHODS: We evaluated 67 children with CLD (38 boys; age 13 [7-18] years) and 37 healthy children to determine the prevalence of MHE. We also assessed the correlation of MHE with changes in brain metabolites by magnetic resonance spectroscopy (1HMRS), diffusion tensor imaging (DTI) derived metrics, blood ammonia and inflammatory cytokines (interleukin-6 [IL6], tumor necrosis factor alpha [TNF-α]). In addition, the accuracy of MR-based investigations for diagnosis of MHE in comparison to neuropsychological tests was analysed. RESULTS: Thirty-four (50.7%) children with CLD had MHE on neuropsychological tests. MHE patients had higher BA (30.5 [6-74] vs. 14 [6-66]µmol/L; p=0.02), IL-6 (8.3 [4.7-28.7] vs. 7.6 [4.7-20.7]pg/ml; p=0.4) and TNF-α (17.8 [7.8-65.5] vs. 12.8 [7.5-35]pg/ml; p=0.06) than No-MHE. 1HMRS showed higher glutamine (2.6 [2.1-3.3] vs. 2.4 [2.0-3.1]; p=0.02), and lower choline (0.20 [0.14-0.25] vs. 0.22 [0.17-0.28]; p=0.1) and myo-inositol (0.25 [0.14-0.41] vs. 0.29 [0.21-0.66]; p=0.2) in MHE patients than those without MHE. Mean diffusivity (MD) on DTI was significantly higher in 6/11 brain areas in patients with MHE vs. no MHE. Brain glutamine had a significant positive correlation with blood ammonia, IL-6, TNF-α and MD of various brain regions. Neuropsychological tests showed a negative correlation with blood ammonia, IL6, TNF-α, glutamine and MD. Frontal white matter MD had a sensitivity and specificity of 73.5% and 100% for diagnosing MHE. CONCLUSIONS: In children with CLD, 50% have MHE. There is a significant positive correlation between markers of hyperammonemia, inflammation and brain edema and these correlate negatively with neuropsychological tests. MD on DTI is a reliable tool for diagnosing MHE. LAY SUMMARY: Fifty percent of children with chronic liver disease develop minimal hepatic encephalopathy (MHE) and perform poorly on neuropsychological testing. These children have raised blood ammonia, inflammatory cytokines and mild cerebral edema on diffusion tensor imaging as compared to children without MHE. The higher the ammonia, inflammatory cytokines and cerebral edema levels the poorer the performance on neuropsychological assessment. The estimation of mean diffusivity on diffusion tensor imaging is an objective and reliable method for diagnosing MHE.
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Encefalopatía Hepática/etiología , Hepatopatías/complicaciones , Adolescente , Encéfalo/metabolismo , Estudios de Casos y Controles , Niño , Enfermedad Crónica , Citocinas/metabolismo , Imagen de Difusión Tensora , Femenino , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/epidemiología , Humanos , India/epidemiología , Espectroscopía de Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , PrevalenciaRESUMEN
Risk stratification, based on the Gleason score (GS) of a prostate biopsy, is an important decision-making tool in prostate cancer management. As low-grade disease may not need active intervention, the ability to identify aggressive cancers on imaging could limit the need for prostate biopsies. We assessed the ability of multiparametric MRI (mpMRI) in pre-biopsy risk stratification of men with prostate cancer. One hundred and twenty men suspected to have prostate cancer underwent mpMRI (diffusion MRI and MR spectroscopic imaging) prior to biopsy. Twenty-six had cancer and were stratified into three groups based on GS: low grade (GS ≤ 6), intermediate grade (GS = 7) and high grade (GS ≥ 8). A total of 910 regions of interest (ROIs) from the peripheral zone (PZ, range 25-45) were analyzed from these 26 patients. The metabolite ratio [citrate/(choline + creatine)] and apparent diffusion coefficient (ADC) of voxels were calculated for the PZ regions corresponding to the biopsy cores and compared with histology. The median metabolite ratios for low-grade, intermediate-grade and high-grade cancer were 0.29 (range: 0.16, 0.61), 0.17 (range: 0.13, 0.32) and 0.13 (range: 0.05, 0.23), respectively (p = 0.004). The corresponding mean ADCs (×10(-3) mm(2) /s) for low-grade, intermediate-grade and high-grade cancer were 0.99 ± 0.08, 0.86 ± 0.11 and 0.69 ± 0.12, respectively (p < 0.0001). The combined ADC and metabolite ratio model showed strong discriminatory ability to differentiate subjects with GS ≤ 6 from subjects with GS ≥ 7 with an area under the curve of 94%. These data indicate that pre-biopsy mpMRI may stratify PCa aggressiveness noninvasively. As the recent literature data suggest that men with GS ≤ 6 cancer may not need radical therapy, our data may help limit the need for biopsy and allow informed decision making for clinical intervention. Copyright © 2015 John Wiley & Sons, Ltd.
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Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Biopsia , Difusión , Humanos , Masculino , Metaboloma , Clasificación del Tumor , Invasividad Neoplásica/diagnóstico por imagen , Curva ROCRESUMEN
BACKGROUND: In vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies on brain in HIV infected patients have shown significant alteration in neuro-biochemicals. METHODS: In this study, we measured the neuro-biochemical metabolites from the left frontal white matter (FWM) and left basal ganglia (BG) caudate head nucleus in 71 subjects that include 30 healthy controls, 20 asymptomatic HIV and 21 HIV patients with CNS lesion. Proton MR spectra were acquired at 3 T MRI system and the concentration (institutional units) of tNAA (N-acetylaspartate, NAA + N-acetylaspartylglutamate, NAAG), tCr (Creatine, Cr + phosphocreatine, PCr), choline containing compounds (tCho), glutamate + glutamine (Glx) and lipid and macromolecules at 0.9 ppm were determined using LC Model. RESULTS: In BG, the concentration of tNAA (6.71 ± 0.64) was decreased and in FWM, the concentration of Glx (20.4 ± 7.8), tCr (9.14 ± 3.04) and lipid and macromolecules at 0.9 ppm (8.69 ± 2.96) were increased in HIV patients with CNS lesion. In healthy controls, the concentration of tNAA in BG was 7.31 ± 0.47 and concentration of Glx, tCr and lipid and macromolecules in FWM were 15.0 ± 6.06, 6.95 ± 2.56, 5.59 ± 1.56, respectively. CONCLUSION: Reduced tNAA in BG suggests neuronal loss in HIV patients with CNS lesion while increased Glx in FWM may suggest excito-toxicity. In addition, increased levels of tCr in FWM of HIV patients were observed. The study indicates region specific metabolic changes in tNAA, tCr and Glx in brain of HIV infected patients.
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Ganglios Basales/metabolismo , Lóbulo Frontal/metabolismo , Infecciones por VIH/metabolismo , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudios de Casos y Controles , Colina/metabolismo , Creatina/metabolismo , Dipéptidos/metabolismo , Femenino , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Humanos , Inositol/metabolismo , Metabolismo de los Lípidos , Sustancias Macromoleculares/metabolismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Espectroscopía de Protones por Resonancia Magnética , Sustancia Blanca/metabolismoRESUMEN
PURPOSE: To investigate the potential of diffusion weighted imaging (DWI) and in vivo proton MR spectroscopy (MRS) in the differentiation of breast tissue of healthy lactating women volunteers and breast cancer patients. MATERIALS AND METHODS: DWI and MRS were carried out at 1.5 Tesla on 12 breast cancer patients and 12 normal lactating women volunteers. Apparent diffusion coefficient (ADC) and total choline (tCho) concentration were determined. RESULTS: tCho was observed in all breast cancer patients and in 10/12 lactating women. Additionally a peak at 3.8 ppm corresponding to lactose was seen in 10/12 of lactating women. Concentration of tCho was similar in malignant breast tissue of patients (3.51 ± 1.72 mmol/kg) and in normal breast tissue of lactating women (3.52 ± 1.70 mmol/kg). However, ADC was significantly higher in the normal breast tissue of lactating women (1.62 ± 0.22 × 10(-3) mm(2)/s) compared with the malignant breast tissue of patients (1.01 ± 0.10 × 10(-3) mm(2)/s). CONCLUSION: Observation of lactose peak with higher ADC in the breast tissue of healthy lactating women volunteers may aid in differentiation of changes that occur in breast tissue due to normal physiological conditions like lactation compared with malignant transformation.
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Neoplasias de la Mama/patología , Imagen de Difusión por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Adulto , Mama/anatomía & histología , Mama/patología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Lactancia , Persona de Mediana Edad , Proyectos Piloto , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND AIM: Celiac disease (CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy. METHODS: Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum test was used. Partial least squares-discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software. RESULTS: Partial least squares-discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy. CONCLUSIONS: NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients.
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Enfermedad Celíaca/metabolismo , Duodeno/metabolismo , Mucosa Intestinal/metabolismo , Espectroscopía de Resonancia Magnética , Adolescente , Adulto , Aminoácidos/metabolismo , Ácido Aspártico/metabolismo , Atrofia , Biomarcadores/metabolismo , Enfermedad Celíaca/diagnóstico , Ciclo del Ácido Cítrico , Duodeno/patología , Femenino , Glucólisis , Humanos , Mucosa Intestinal/patología , Isoleucina/metabolismo , Leucina/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Protones , Ácido Pirúvico/metabolismo , Ácido Succínico/metabolismo , Adulto JovenRESUMEN
High-resolution NMR spectroscopic studies of prostate tissue extracts, prostatic fluid, seminal fluid, serum and urine can be used for the detection of prostate cancer, based on the differences in their metabolic profiles. Useful diagnostic information is obtained by the detection or quantification of as many metabolites as possible and comparison with normal samples. Only a few studies have shown the potential of high-resolution in vitro NMR of prostate tissues. A survey of the literature has revealed that studies on body fluids, such as urine and serum, in relation to prostate cancer are rare. In addition, the potential of NMR of nuclei other than (1)H, such as (13)C and (31)P, has not been exploited fully. The metabolomic analysis of metabolites, detected by high-resolution NMR, may help to identify metabolites which could serve as useful biomarkers for prostate cancer detection. Such NMR-derived biomarkers would not only help in prostate cancer detection and in understanding the in vivo MRS metabolic profile, but also to investigate the biochemical and metabolic changes associated with cancer. Here, we review the published research work on body fluids in relation to prostate and prostate tissue extracts, and highlight the potential of such studies for future work.